The purpose of this research project is to determine if Fatigue: Take Control (FTC), a formal multi-modal program owned and distributed by the National Multiple Sclerosis (MS) Society (NMSS) based on the Fatigue and MS clinical practice guideline, is effective in reducing fatigue in Veterans and others with MS. The specific objectives are: 1) To determine if FTC reduces fatigue in non-depressed ambulatory people with MS at the end of the intervention and at 3, 6 and 12 months after the intervention compared to a general MS group education program on the Modified Fatigue Impact Scale, the primary outcome measure; 2) To determine if FTC increases self-efficacy compared to a general MS group education program in people with MS as measured by the MS Self-Efficacy Scale; 3) To determine if FTC results in subjects reporting a) changes in medication utilization using a self-report medication diary, b) exercise participatio using the self-report Rapid Assessment of Physical Activity and c) quality of life using the SF-36, and 4) To determine if FTC objectively increases activity participation compared to a general MS group education program using the StepWatch Activity Monitors (SAM). 200 subjects will be enrolled (100 per arm) with 50 at each of four VA sites - Portland, Seattle, Baltimore and Gainesville - for a randomized single blind controlled parallel treatment trial with two arms. It i important to conduct this trial at a minimum of 4 sites to establish that the program is effective t different locations, with different moderators, with an appropriate control intervention to control for socialization and content, and to ensure rapid enrollment. Subjects will be randomized to participate either in the FTC (includes DVD viewing, discussion, homework and workbooks) or a general MS education program not addressing fatigue (includes discussion and NMSS produced materials). Subjects will attend weekly two-hour group classes for 6 weeks with primary outcome data collected at baseline and one week after completing the classes. At 3 months and 6 months following completion of their respective programs, subjects will undergo repeat evaluations to assess for durability of responses and then will exit the study. Subjects wil be recruited from the VA MS Clinics, the MS Clinics at the affiliated medical schools and the community to assure participation of women and minorities. The SD of difference from baseline MFIS in the pilot study was about 10. This means that groups of about 40 each would provide power of 80% for detecting the clinically meaningful change of 7 units. However, the present study involves comparison of the immediate change from baseline to that several months later, involving more variation with a SD in the pilot study of 16 rather than 10. Power for detecting change of 7 units, using centers of 40 subjects each will provide 80% power of finding significant change at the 5% level with a 2-sided test. We plan to enroll 50 subjects at each site with the goal of retaining at least 40 with reimbursement for time and travel in addition to the quality of the programs. For the primary endpoint analysis, ordinary (i.e. least squares) multiple regression analysis will be employed, stratifying on center, and adjusting for covariates using a binary indicator variable for treatment. The other aspect of the primary aim involves assessing maintenance of any improvement in follow-ups at 3 and 6 months. Changes for individuals will also be used for this: change from baseline for the immediate effect, and change from the end of course for the follow-up effects at 3 and 6 months. We anticipate requiring 48 months for this research project: 12 months to initiate the trial including centralized staff training and purchasig the StepWatch Activity Monitors, 24 months to fully enroll the study, six additional months to complete the trial and six months to complete analysis of the results. The critical staff requiring salary support will be the Co-Investigator, four Site Coordinators, four consulting MS nurses and four consulting MS physical or occupational therapists (one each at each site). The estimated budget will be $1,160,000 over the four years of the study. PUBLIC HEALTH RELEVANCE: Multiple sclerosis (MS) affects approximately 2.5 million people worldwide and approximately 400,000 Americans. Fatigue occurs in 75-95% of people with MS and is often their most disabling symptom. There are over 6,000 Veterans who are service connected for MS and approximately 20,000 Veterans with MS receive care through Veterans Health Administration (VHA) in any one year. Currently the VHA spends $274 million treating Veterans with MS at an average cost per patient per year of $19,875. Fatigue limits day to day function, participation in family and community and health related quality of life. With few symptomatic therapies, demonstrating that any new treatment for fatigue in MS is effective would be a significant innovation to improve care. Should we demonstrate in this randomized well-powered trial with appropriate controls that Fatigue: Take Control (FTC) is effective, there will be an educational program with proven efficacy to offer Veterans with MS. FTC is available at all NMSS chapters and all VAMC for cost-effective implementation.